title: Amyloid-β load predicts medial temporal lobe dysfunction in Alzheimer dementia.
abstract: Amyloid-β (Aβ) deposition is a pathologic hallmark of Alzheimer disease (AD). Although the typical spatial distribution pattern of Aβ deposition in early AD mainly involves regions distant from the hippocampus, the predominant clinical feature is impairment of hippocampus-dependent memory. We aimed at elucidating the relationship between neocortical Aβ load, regional neuronal function, and memory impairment.
  
  
  METHODS
  Thirty patients with early AD underwent combined (11)C-Pittsburgh compound B ((11)C-PIB) and (18)F-FDG PET and memory assessments. Composite measures of hemispheric Aβ load were calculated by volume-weighted mean values of neocortical (11)C-PIB binding. Voxelwise (18)F-FDG uptake was used as a measure of regional glucose metabolism reflecting neuronal activity. We investigated the relationship between left- and right-hemispheric Aβ load and regional glucose metabolism (voxelwise analyses). In addition, we assessed the correlations of hemispheric Aβ load (region-of-interest-based analyses) and regional glucose metabolism (voxelwise analysis) with memory performance. Analyses were corrected for age and sex.
  
  
  RESULTS
  Higher Aβ load in the left hemisphere was associated with reduced glucose metabolism of the left medial temporal lobe (MTL; r(2) = 0.38) and correlated with worse wordlist recall (r = -0.37; partial correlation controlled for sex and age). Furthermore, wordlist recall correlated with regional glucose metabolism in the bilateral MTL and precuneus-posterior cingulate cortex and right lingual gyrus (r(2) = 0.24).
  
  
  CONCLUSIONS
  We demonstrated an association between the left-hemispheric Aβ load and impairment of the left MTL in AD at 2 different levels: regional hypometabolism and verbal memory. This correlation suggests that neocortical amyloid deposition is connected to or even drives neuronal dysfunction and neurodegeneration of the MTL, which is associated with impaired episodic memory processing as a clinical core symptom of AD.
authors.affiliation: Center of Geriatrics and Gerontology Freiburg, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Frings
authors.forename: Timo S
authors.initials: TS
authors.lastname: Spehl
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008568:Memory; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: Alzheimer’s disease; Pittsburgh compound B; amyloid; episodic memory; positron emission tomography